Is it possible to generalise superspreading individuals or events of SARS-CoV-2? – Authors' reply
Authors: Jie Zhou, Anika Singanayagam, Wendy S Barclay
Journal: The Lancet Microbe (2023)

We thank Sunil Shrestha and colleagues for their interest in our Article reporting data on virus emitted by participants in the world's first SARS-CoV-2 human challenge study.1Zhou J Singanayagam A Goonawardane N et al.Viral emissions into the air and environment after SARS-CoV-2 human challenge: a phase 1, open label, first-in-human study.Lancet Microbe. 2023; 4: e579-e590Summary Full Text Full Text PDF Scopus (0) Google Scholar We understand their concerns about the generalisability of the results due to the small sample size (n=18 infected participants) and demographic diversity. Indeed, we have highlighted these limitations in our paper. A strength of our study is the ability to measure emissions longitudinally and intensively, from the onset of infection, which is difficult to achieve in a field study. We therefore consider the unique data obtained through this human challenge study very valuable in furthering our understanding of infectiousness and transmission. Certainly, this must be considered alongside data obtained through other study designs. Challenge studies are resource-intensive and expensive to conduct; moreover, the benefits must be weighed up alongside potential risks to participants and others. We discuss these issues further in a Lancet Microbe podcast accompanying our Article1Zhou J Singanayagam A Goonawardane N et al.Viral emissions into the air and environment after SARS-CoV-2 human challenge: a phase 1, open label, first-in-human study.Lancet Microbe. 2023; 4: e579-e590Summary Full Text Full Text PDF Scopus (0) Google Scholar and in a previous publication.2Rapeport G Smith E Gilbert A Catchpole A McShane H Chiu C SARS-CoV-2 human challenge studies—establishing the model during an evolving pandemic.N Engl J Med. 2021; 385: 961-964Crossref Scopus (24) Google Scholar In this first SARS-CoV-2 human challenge study, the sample size was not expanded beyond n=36 because the primary endpoint of the study (to assess safety, and to initiate mild infection in >50% of participants) was achieved. The full study protocol and a peer-reviewed paper describing safety and viral kinetics after SARS-CoV-2 human challenge have been published.3Killingley B Mann AJ Kalinova M et al.Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge in young adults.Nat Med. 2022; 28: 1031-1041Crossref PubMed Scopus (123) Google Scholar We agree that a diverse range of research methods and patient groups is crucial for gaining a comprehensive understanding of the complexities of SARS-CoV-2 transmission. Our team has also conducted air and environmental sampling in various real-world settings, including households,4Cordery R Reeves L Zhou J et al.Transmission of SARS-CoV-2 by children to contacts in schools and households: a prospective cohort and environmental sampling study in London.Lancet Microbe. 2022; 3: e814-e823Summary Full Text Full Text PDF PubMed Google Scholar public transport,5Transport for LondonCoronavirus publications. Publications and reports related to coronavirus and TfL's response to it.https://tfl.gov.uk/corporate/publications-and-reports/coronavirus-publicationsDate: 2022Date accessed: July 26, 2023Google Scholar a university campus, student accommodation, and general hospital wards.6Zhou J Otter JA Price JR et al.Investigating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surface and air contamination in an acute healthcare setting during the peak of the coronavirus disease 2019 (COVID-19) pandemic in London.Clin Infect Dis. 2021; 73: e1870-e1877Crossref PubMed Scopus (143) Google Scholar, 7Winslow RL Zhou J Windle EF et al.SARS-CoV-2 environmental contamination from hospitalised patients with COVID-19 receiving aerosol-generating procedures.Thorax. 2022; 77: 259-267Crossref PubMed Scopus (23) Google Scholar These studies included participants with a range of demographics, age groups, comorbidities, and illness severity. We collected air samples from hospitalised patients with COVID-19 requiring supplemental oxygen; patients were aged 35–75 years and some had comorbidities.7Winslow RL Zhou J Windle EF et al.SARS-CoV-2 environmental contamination from hospitalised patients with COVID-19 receiving aerosol-generating procedures.Thorax. 2022; 77: 259-267Crossref PubMed Scopus (23) Google Scholar Additionally, we have collected emissions in households, including children aged 2–18 years with COVID-19.4Cordery R Reeves L Zhou J et al.Transmission of SARS-CoV-2 by children to contacts in schools and households: a prospective cohort and environmental sampling study in London.Lancet Microbe. 2022; 3: e814-e823Summary Full Text Full Text PDF PubMed Google Scholar Notably, the quantities of airborne virus we measured in these real-life situations were similar to those measured in the human challenge study (appendix). Together, these data help to improve confidence that the observations we report from the human challenge study are in line with results observed more widely. Nonetheless, we support the need for further studies in a diversity of settings to help answer the many remaining unknowns around SARS-CoV-2 transmission, which are critical for public health, including a better understanding of superspreading. Further SARS-CoV-2 human challenge studies are planned, which will recruit vaccinated people and inoculate them with more recent variants.8Imperial College LondonCOVID-19 Human Challenge Study: COVHIC002.https://www.imperial.ac.uk/infectious-disease/research/human-challenge/covhic002/Date: 2023Date accessed: August 4, 2023Google Scholar We hope that our ongoing research will continue to contribute to understanding about SARS-CoV-2 emissions and transmission dynamics. We declare no competing interests. Download .pdf (.16 MB) Help with pdf files Supplementary appendix Viral emissions into the air and environment after SARS-CoV-2 human challenge: a phase 1, open label, first-in-human studyAfter controlled experimental inoculation, the timing, extent, and routes of viral emissions was heterogeneous. We observed that a minority of participants were high airborne virus emitters, giving support to the notion of superspreading individuals or events. Our data implicates the nose as the most important source of emissions. Frequent self-testing coupled with isolation upon awareness of first symptoms could reduce onward transmissions. Full-Text PDF Open AccessIs it possible to generalise superspreading individuals or events of SARS-CoV-2?Jie Zhou and colleagues reported data indicating the potential for superspreading individuals or events that contribute to SARS-CoV-2 emissions into the air and the environment following human exposure to the virus.1 This research contributes significantly to understanding the disease's transmission dynamics, highlighting the importance of nasal emissions, hand hygiene, surface cleaning, self-testing, and early symptom recognition. However, careful consideration must be given to the study's limitations, particularly in generalising the results, with three viewpoints to consider. Full-Text PDF Open Access